To evaluate prognostic and therapeutic significance, tumor DNA content was determined by flow cytometry in 310 paraffin-embedded tissue samples obtained surgically from 130 patients with non-small cell lung cancer. Ninety-six (76.8%) patients had DNA aneuploid patterns that were statistically higher in adenocarcinoma than in squamous cell carcinoma. A better 5-year survival rate was observed in Group A (DNA diploidy, 69.6%) than in Group B (DNA aneuploidy and DNA peridiploidy, 33.2%; P less than 0.001). The survival curves of the patients in Group B continued to decrease during the next 2.5 years. Cox's model analysis showed that both the pathologic stage and the DNA content were the significant prognostic factors for survival. However, the DNA content was an independent prognostic factor in squamous cell carcinoma, but not in adenocarcinoma. These results indicate that DNA content analysis is useful for the evaluation of clinical behavior and prognosis, and that the clinical value of the DNA content must be differentiated between squamous cell carcinoma and adenocarcinoma.